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Effects of Prenatal Exposure to a Mixture of Organophosphate Flame Retardants on Placental Gene Expression and Serotonergic Innervation in the Fetal Rat Brain.

Publication ,  Journal Article
Rock, KD; St Armour, G; Horman, B; Phillips, A; Ruis, M; Stewart, AK; Jima, D; Muddiman, DC; Stapleton, HM; Patisaul, HB
Published in: Toxicological sciences : an official journal of the Society of Toxicology
July 2020

There is a growing need to understand the potential neurotoxicity of organophosphate flame retardants (OPFRs) and plasticizers because use and, consequently, human exposure, is rapidly expanding. We have previously shown in rats that developmental exposure to the commercial flame retardant mixture Firemaster 550 (FM 550), which contains OPFRs, results in sex-specific behavioral effects, and identified the placenta as a potential target of toxicity. The placenta is a critical coordinator of fetal growth and neurodevelopment, and a source of neurotransmitters for the developing brain. We have shown in rats and humans that flame retardants accumulate in placental tissue, and induce functional changes, including altered neurotransmitter production. Here, we sought to establish if OPFRs (triphenyl phosphate and a mixture of isopropylated triarylphosphate isomers) alter placental function and fetal forebrain development, with disruption of tryptophan metabolism as a primary pathway of interest. Wistar rat dams were orally exposed to OPFRs (0, 500, 1000, or 2000 μg/day) or a serotonin (5-HT) agonist 5-methoxytryptamine for 14 days during gestation and placenta and fetal forebrain tissues collected for analysis by transcriptomics and metabolomics. Relative abundance of genes responsible for the transport and synthesis of placental 5-HT were disrupted, and multiple neuroactive metabolites in the 5-HT and kynurenine metabolic pathways were upregulated. In addition, 5-HTergic projections were significantly longer in the fetal forebrains of exposed males. These findings suggest that OPFRs have the potential to impact the 5-HTergic system in the fetal forebrain by disrupting placental tryptophan metabolism.

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Published In

Toxicological sciences : an official journal of the Society of Toxicology

DOI

EISSN

1096-0929

ISSN

1096-6080

Publication Date

July 2020

Volume

176

Issue

1

Start / End Page

203 / 223

Related Subject Headings

  • Toxicology
  • Serotonin
  • Rats, Wistar
  • Rats
  • Prenatal Exposure Delayed Effects
  • Pregnancy
  • Polybrominated Biphenyls
  • Plasticizers
  • Placenta
  • Organophosphorus Compounds
 

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Rock, K. D., St Armour, G., Horman, B., Phillips, A., Ruis, M., Stewart, A. K., … Patisaul, H. B. (2020). Effects of Prenatal Exposure to a Mixture of Organophosphate Flame Retardants on Placental Gene Expression and Serotonergic Innervation in the Fetal Rat Brain. Toxicological Sciences : An Official Journal of the Society of Toxicology, 176(1), 203–223. https://doi.org/10.1093/toxsci/kfaa046
Rock, Kylie D., Genevieve St Armour, Brian Horman, Allison Phillips, Matthew Ruis, Allison K. Stewart, Dereje Jima, David C. Muddiman, Heather M. Stapleton, and Heather B. Patisaul. “Effects of Prenatal Exposure to a Mixture of Organophosphate Flame Retardants on Placental Gene Expression and Serotonergic Innervation in the Fetal Rat Brain.Toxicological Sciences : An Official Journal of the Society of Toxicology 176, no. 1 (July 2020): 203–23. https://doi.org/10.1093/toxsci/kfaa046.
Rock KD, St Armour G, Horman B, Phillips A, Ruis M, Stewart AK, et al. Effects of Prenatal Exposure to a Mixture of Organophosphate Flame Retardants on Placental Gene Expression and Serotonergic Innervation in the Fetal Rat Brain. Toxicological sciences : an official journal of the Society of Toxicology. 2020 Jul;176(1):203–23.
Rock, Kylie D., et al. “Effects of Prenatal Exposure to a Mixture of Organophosphate Flame Retardants on Placental Gene Expression and Serotonergic Innervation in the Fetal Rat Brain.Toxicological Sciences : An Official Journal of the Society of Toxicology, vol. 176, no. 1, July 2020, pp. 203–23. Epmc, doi:10.1093/toxsci/kfaa046.
Rock KD, St Armour G, Horman B, Phillips A, Ruis M, Stewart AK, Jima D, Muddiman DC, Stapleton HM, Patisaul HB. Effects of Prenatal Exposure to a Mixture of Organophosphate Flame Retardants on Placental Gene Expression and Serotonergic Innervation in the Fetal Rat Brain. Toxicological sciences : an official journal of the Society of Toxicology. 2020 Jul;176(1):203–223.
Journal cover image

Published In

Toxicological sciences : an official journal of the Society of Toxicology

DOI

EISSN

1096-0929

ISSN

1096-6080

Publication Date

July 2020

Volume

176

Issue

1

Start / End Page

203 / 223

Related Subject Headings

  • Toxicology
  • Serotonin
  • Rats, Wistar
  • Rats
  • Prenatal Exposure Delayed Effects
  • Pregnancy
  • Polybrominated Biphenyls
  • Plasticizers
  • Placenta
  • Organophosphorus Compounds